Anti-tumor-promoting effects of phenylpropanoids on Epstein–Barr virus activation and two-stage mouse skin carcinogenesis

In our joint project in the search for anti-tumor promoters from natural plant sources, we carried out a primary screening of 12 phenylpropanoids isolated from Boronia pinnata Sm. (Rutaceae) by examining their possible inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All tested compounds in this study showed inhibitory activity against the EBV activation even at 1×10 mol ratio without any cytotoxicity. Among 12 phenylpropanoids tested, boropinal-C (1), boropinol-A (5), boropinol-C (9) and 3-(3′-methoxy-4′-prenyloxy)phenyl-1-propene (10), all having a 4′-(3-methylbut-2-enyloxy) group, a so-called prenyloxy group, showed more potent activities. Furthermore, 3-(3′-methoxy-4′-prenyloxy)phenyl-1-propene (10) also exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. This investigation indicated that certain phenylpropanoids might be valuable anti-tumor promoters.